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Updated: May 8, 2026
A Workflow to Quantitatively Determine Age-Related Macular Degeneration Lesion-Specific Variations in Fundus Autofluorescence
Published on: May 26, 2023
Clinical and molecular analysis of Stargardt disease with preserved foveal structure and function
Kaoru Fujinami1, Panagiotis I Sergouniotis2, Alice E Davidson2
1University College London, Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom; Laboratory of Visual Physiology, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan; Department of Ophthalmology, Keio University, School of Medicine, Tokyo, Japan.
Purpose:
To describe a cohort of patients with Stargardt disease who show a foveal-sparing phenotype.
Design:
Retrospective case series.
Methods:
The foveal-sparing phenotype was defined as foveal preservation on autofluorescence imaging, despite a retinopathy otherwise consistent with Stargardt disease. Forty such individuals were ascertained and a full ophthalmic examination was undertaken. Following mutation screening of ABCA4, the molecular findings were compared with those of patients with Stargardt disease but no foveal sparing.
Results:
The median age of onset and age at examination of 40 patients with the foveal-sparing phenotype were 43.5 and 46.5 years. The median logMAR visual acuity was 0.18. Twenty-two patients (22/40, 55%) had patchy parafoveal atrophy and flecks; 8 (20%) had numerous flecks at the posterior pole without atrophy; 7 (17.5%) had mottled retinal pigment epithelial changes; 2 (5%) had multiple atrophic lesions, extending beyond the arcades; and 1 (2.5%) had a bull's-eye appearance. The median central foveal thickness assessed with spectral-domain optical coherence tomographic images was 183.0 μm (n = 33), with outer retinal tubulation observed in 15 (45%). Twenty-two of 33 subjects (67%) had electrophysiological evidence of macular dysfunction without generalized retinal dysfunction. Disease-causing variants were found in 31 patients (31/40, 78%). There was a higher prevalence of the variant p.Arg2030Gln in the cohort with foveal sparing compared to the group with foveal atrophy (6.45% vs 1.07%).
Conclusions:
The distinct clinical and molecular characteristics of patients with the foveal-sparing phenotype are described. The presence of 2 distinct phenotypes of Stargardt disease (foveal sparing and foveal atrophy) suggests that there may be more than 1 disease mechanism in ABCA4 retinopathy.
